Sinapine as an active compound for inhibiting the proliferation of Caco-2 cells via downregulation of P-glycoprotein
2014
Guo, Ying | An, Hongli | Feng, Liuxin | Liu, Qi | Wang, Sicen | Zhang, Tao
Sinapine, an alkaloid from seeds of the cruciferous species, shows favorable biological activities such as antioxidant and radio-protective activities. However, the inhibitory effect of sinapine on tumors, and the molecular mechanisms have not been completely understood thus far. In this study, we determined anti-proliferative effects of sinapine. We examined the anti-tumor effects of the combination of sinapine and doxorubicin. The results of the MTT assay and apoptosis showed that sinapine increased the sensitivity of Caco-2 cells to doxorubicin in a dose-dependent manner, whereas no or less effect was observed in the cells treated with doxorubicin alone. The combination of sinapine and doxorubicin had a synergistic effect and increased the cytotoxicity of doxorubicin against Caco-2 cells. Doxorubicin accumulation assay showed that sinapine increased the intracellular accumulation of doxorubicin in dose-dependent manner. Immunoblotting and QT-PCR analysis showed that sinapine suppressed P-glycoprotein (P-gp) expression via ubiquitination. A significant correlation was observed between the expression of p-ERK1/2 and P-gp. These results indicated that sinapine played an important role in the down-regulation of P-gp expression through suppression of FGFR4-FRS2α-ERK1/2 signaling pathway. To our knowledge, this is the first study to show that sinapine can be used as an effective natural compound for chemo-resistance.
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